Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000733851 | SCV000617818 | uncertain significance | not provided | 2017-10-19 | criteria provided, single submitter | clinical testing | The c.61 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.61 G>A variant is observed in 20/126,456 (0.02%) alleles from individuals of European background (Lek et al., 2016). Multiple in-silico splice prediction models predict that c.61 G>A enhances a cryptic splice donor site which may supplant the natural donor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies the actual effect of c.61 G>A on splicing in this individual is unknown. If c.61 G>A does not alter splicing, it will result in the E21K missense change. The E21K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, most reported pathogenic variants in the NEB gene are truncating/loss-of-function. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Invitae | RCV000550343 | SCV000640840 | uncertain significance | Nemaline myopathy 2 | 2019-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 21 of the NEB protein (p.Glu21Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs199907781, ExAC 0.01%). This variant has not been reported in the literature in individuals with NEB-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
EGL Genetic Diagnostics, |
RCV000733851 | SCV000861952 | uncertain significance | not provided | 2018-06-13 | criteria provided, single submitter | clinical testing | |
Hudson |
RCV000550343 | SCV000993627 | uncertain significance | Nemaline myopathy 2 | 2019-03-15 | criteria provided, single submitter | research | |
Natera, |
RCV000550343 | SCV001458316 | uncertain significance | Nemaline myopathy 2 | 2020-01-17 | no assertion criteria provided | clinical testing |